array:24 [ "pii" => "S225380892100080X" "issn" => "22538089" "doi" => "10.1016/j.remnie.2021.04.009" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "1287" "copyright" => "Sociedad Española de Medicina Nuclear e Imagen Molecular" "copyrightAnyo" => "2021" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Rev Esp Med Nucl Imagen Mol. 2022;41 Supl 1:S22-S23" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S2253654X21000640" "issn" => "2253654X" "doi" => "10.1016/j.remn.2021.03.006" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "1287" "copyright" => "Sociedad Española de Medicina Nuclear e Imagen Molecular" "documento" => "article" "crossmark" => 1 "subdocumento" => "sco" "cita" => "Rev Esp Med Nucl Imagen Mol. 2022;41 Supl 1:S22-S23" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">IMÁGENES DE INTERÉS</span>" "titulo" => "Captación de <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE en la Displasia Fibrosa Poliostótica con Síndrome de McCune-Albright" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S22" "paginaFinal" => "S23" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "<span class="elsevierStyleSup">68</span>Ga-DOTA-TATE uptake in polyostotic fibrous dysplasia with McCune-Albright syndrome" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figura 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1966 "Ancho" => 2007 "Tamanyo" => 297035 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">La MIP coronal (A), la TC coronal (B) y la PET/TC con <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE (C) mostraron lesiones expansivas de DF que afectaban a múltiples costillas, los huesos ilíacos y el fémur izquierdo, con escoliosis lumbar. Cabe destacar el aspecto benigno de estas lesiones DF con destrucción geográfica con las corticales intactas y los márgenes bien definidos. Estas lesiones tienen una captación entre leve y moderada de <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE (SUV<span class="elsevierStyleInf">máx</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4,88) en las imágenes de PET, que indica una disminución relativa de la actividad de la enfermedad durante la edad adulta. Las imágenes de TC axial (D) y PET/TC con <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE axial fusionadas (E) también mostraron una captación extensa y difusa que involucraba la mayor parte del cráneo y los huesos faciales, con una apariencia mixta que correlacionaba con la captación entre leve y moderada de <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE. La captación intensa de <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE (SUV<span class="elsevierStyleInf">máx</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>10,0), que estaba por encima de la SUV<span class="elsevierStyleInf">máx</span> del hígado, dentro de la silla turca, se evaluó como secundaria a las características de la acromegalia además de a la actividad fisiológica de la glándula pituitaria. Además, la PET/TC axial con <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE (F y G) representó el aumento de la captación del péptido DOTA (SUV<span class="elsevierStyleInf">máx</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6,4) en la gran masa en la cola pancreática, consistente con la recurrencia local (punta de flecha). No hubo captación de este radiotrazador en las grandes lesiones hipodensas hepáticas, que se evaluaron como quistes debido a sus características en la resonancia magnética.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "K. Niftaliyeva, H.T. Turoglu, T. Ones, S. Kesim, T.Y. Erdil" "autores" => array:5 [ 0 => array:2 [ "nombre" => "K." "apellidos" => "Niftaliyeva" ] 1 => array:2 [ "nombre" => "H.T." "apellidos" => "Turoglu" ] 2 => array:2 [ "nombre" => "T." "apellidos" => "Ones" ] 3 => array:2 [ "nombre" => "S." "apellidos" => "Kesim" ] 4 => array:2 [ "nombre" => "T.Y." "apellidos" => "Erdil" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S225380892100080X" "doi" => "10.1016/j.remnie.2021.04.009" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S225380892100080X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2253654X21000640?idApp=UINPBA00004N" "url" => "/2253654X/00000041000000S1/v1_202207160644/S2253654X21000640/v1_202207160644/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2253808921000811" "issn" => "22538089" "doi" => "10.1016/j.remnie.2021.04.010" "estado" => "S300" "fechaPublicacion" => "2022-01-01" "aid" => "1288" "copyright" => "Sociedad Española de Medicina Nuclear e Imagen Molecular" "documento" => "article" 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"etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 761 "Ancho" => 2925 "Tamanyo" => 161635 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The axial SPECT/CT revealed aspiration pneumonia.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Yuxiao Xia, YuHong Shi, Quanyu Zhou, Yue Chen" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Yuxiao" "apellidos" => "Xia" ] 1 => array:2 [ "nombre" => "YuHong" "apellidos" => "Shi" ] 2 => array:2 [ "nombre" => "Quanyu" "apellidos" => "Zhou" ] 3 => array:2 [ "nombre" => "Yue" "apellidos" => "Chen" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S2253654X21000652" "doi" => "10.1016/j.remn.2021.03.007" 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"gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Interesting images</span>" "titulo" => "Diffuse large B-cell lymphoma detected by Al<span class="elsevierStyleSup">18</span>F-NOTA-FAPI-04 PET/CT" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S20" "paginaFinal" => "S21" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Linfoma difuso de células B grandes detectado por PET/TC Al<span class="elsevierStyleSup">18</span>F-NOTA-FAPI-04" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 3262 "Ancho" => 2925 "Tamanyo" => 665187 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A cavity without enhancement in the left parietal lobe (A–C). A mass was found in corpus callosum and the left temporal lobe with homogeneous enhancement (D–I).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Xiaojuan Peng, Yutang Yao, Xiao Jiang, Xing Zhou, Chuan Li, Zhuzhong Cheng" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Xiaojuan" "apellidos" => "Peng" ] 1 => array:2 [ "nombre" => "Yutang" "apellidos" => "Yao" ] 2 => array:2 [ "nombre" => "Xiao" "apellidos" => "Jiang" ] 3 => array:2 [ "nombre" => "Xing" "apellidos" => "Zhou" ] 4 => array:2 [ "nombre" => "Chuan" "apellidos" => "Li" ] 5 => array:2 [ "nombre" => "Zhuzhong" "apellidos" => "Cheng" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S2253654X21000615" "doi" => "10.1016/j.remn.2021.03.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2253654X21000615?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S225380892100077X?idApp=UINPBA00004N" "url" => "/22538089/00000041000000S1/v1_202207210552/S225380892100077X/v1_202207210552/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Interesting images</span>" "titulo" => "<span class="elsevierStyleSup">68</span>Ga-DOTA-TATE uptake in polyostotic fibrous dysplasia with McCune-Albright syndrome" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S22" "paginaFinal" => "S23" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Khanim Niftaliyeva, Halil Turgut Turoglu, Tunc Ones, Selin Kesim, Tanju Yusuf Erdil" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Khanim" "apellidos" => "Niftaliyeva" ] 1 => array:4 [ "nombre" => "Halil Turgut" "apellidos" => "Turoglu" "email" => array:1 [ 0 => "turgutturoglu@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 2 => array:2 [ "nombre" => "Tunc" "apellidos" => "Ones" ] 3 => array:2 [ "nombre" => "Selin" "apellidos" => "Kesim" ] 4 => array:2 [ "nombre" => "Tanju Yusuf" "apellidos" => "Erdil" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Department of Nuclear Medicine, Marmara University School of Medicine, Istanbul, Turkey" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Captación de <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE en la Displasia Fibrosa Poliostótica con Síndrome de McCune-Albright" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2577 "Ancho" => 1508 "Tamanyo" => 174510 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Bone scintigraphy revealed intense <span class="elsevierStyleSup">99m</span>Tc-MDP uptake in lytic/sclerotic expansile lesions including calvaria, ribs, sternum, pelvis, right humerus, right forearm, hand, femora, right tibia and foot compatible with polyostotic fibrous dysplasia lesions. In addition, <span class="elsevierStyleSup">99m</span>Tc-MDP uptake was noted on the lower sternum, which was related to an insufficiency bone fracture secondary to fibrous dysplasia lesions.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">A 38-year-old man with McCune-Albright syndrome (MAS) and acromegaly was diagnosed with polyostotic fibrous dysplasia (FD) two years ago. Bone scintigraphy revealed intense <span class="elsevierStyleSup">99m</span>Tc-MDP uptake in multiple lytic/sclerotic expansile lesions (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>). He was referred for <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE PET/CT scan to monitor his response to chemotherapy and radiation therapy of a resected pancreatic tail neuroendocrine tumor. The PET/CT was not only consistent with local recurrence; but also demonstrated mild to moderately increased <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE uptake involving multiple bones, thus mimicking osseous metastases. However, the CT component of the PET/CT study revealed multiple expansile lucent/ground-glass opacity and/or sclerotic lesions consistent with the known polyostotic FD (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0010" class="elsevierStylePara elsevierViewall">Although the lesions are usually unilateral in polyostotic FD, they may be bilateral as shown in this case. Craniofacial FD lesions become more heterogeneous on CT with increasing age, with development of lucent cystic lesions (just like this case); as compared to the homogeneous ground-glass opacity seen in childhood. Our findings are congruent with Octreoscan findings reported by Chen et al. showing abnormally increased pentetreotide (somatostatin analogue) uptake in FD lesions in a similar case of MAS.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> FD is a rare, benign bone disease due to sporadic mutation of the alpha-subunit of Gs stimulatory protein (GNAS mutations) resulting in activation and overproduction of cyclic adenosine monophosphate (cAMP). MAS is the triad of polyostotic FD with extraskeletal manifestations like “café-au-lait” skin macules and endocrine disease(s) such as precocious puberty and/or growth hormone excess which is present in our case. Studies demonstrate an excellent correlation between SUV on <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE PET/CT and somatostatin receptor subtype 2 (SSTR 2) expression as determined by reverse polymerase chain reaction. Mackie et al. reported osteoblastic bony diseases to show <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE uptake since osteoblasts express SSTR 2.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Degenerative bone disease, fractures, fibrous dysplasia, vertebral hemangiomas, and growth plates in infancy and childhood, all show <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE uptake, but these entities may be easily differentiated from pathologic activity due to their low intensity uptake and consistent features on the CT component of the study.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">68</span>Ga-DOTA-TATE (i.e. SSTR) overexpression in polyostotic FD may be confused with multifocal metastatic disease, as both have multiple sites of increased osseous uptake. The differential diagnosis of bony metastases on <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE PET includes not only polyostotic forms of benign bone diseases like FD and Paget Disease; but also their malignant transformation, especially in the clinical setting of neuroendocrine tumors. Another challenge is their co-existence. The presented case also implies the application of PET/CT imaging with <span class="elsevierStyleSup">68</span>Ga-DOTA peptides in assessing and monitoring the extent and activity of FD with the possibility of prognostic evaluation.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interests</span><p id="par0015" class="elsevierStylePara elsevierViewall">All the authors state that there were no conflicts of interests when the manuscript was written.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interests" ] 1 => array:2 [ "identificador" => "xack617731" "titulo" => "Acknowledgement" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Niftaliyeva K, Turoglu HT, Ones T, Kesim S, Erdil TY. Captación de <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE en la Displasia Fibrosa Poliostótica con Síndrome de McCune-Albright. Rev Esp Med Nucl Imagen Mol. 2022;41:S22–S23.</p>" ] ] "multimedia" => array:2 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2577 "Ancho" => 1508 "Tamanyo" => 174510 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Bone scintigraphy revealed intense <span class="elsevierStyleSup">99m</span>Tc-MDP uptake in lytic/sclerotic expansile lesions including calvaria, ribs, sternum, pelvis, right humerus, right forearm, hand, femora, right tibia and foot compatible with polyostotic fibrous dysplasia lesions. In addition, <span class="elsevierStyleSup">99m</span>Tc-MDP uptake was noted on the lower sternum, which was related to an insufficiency bone fracture secondary to fibrous dysplasia lesions.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1748 "Ancho" => 1755 "Tamanyo" => 243835 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Coronal MIP (A), Coronal CT (B) and <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE PET/CT (C) depicted expansile FD lesions involving multiple ribs, the iliac bones, left femur with lumbar scoliosis. The benign appearances of these FD lesions with geographic destruction with intact cortices and well-defined margins was noteworthy. These lesions have mild-to-moderate <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE uptake (SUVmax<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4.88) on PET images suggesting relative decrease in disease activity during adulthood. Axial CT (D) and fused PET/CT (E) images also demonstrated extensive and diffuse FD involving most of the skull and facial bones with a mixed appearance correlating mild-to-moderate <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE uptake. Intense <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE uptake (SUVmax<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>10.0), which was above the SUVmax of the liver, within the sella turcica was evaluated as secondary to the acromegaly feature in addition to the physiological pituitary gland activity. In addition, the axial <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE PET/CT (F and G) depicted increased DOTA peptide uptake (SUV max: 6.4) in the large mass at the pancreatic tail, consistent with local recurrence (arrowhead). There was no <span class="elsevierStyleSup">68</span>Ga-DOTA-TATE uptake in the large hepatic hypodense lesions, which were evaluated as cysts due to their characteristic magnetic resonance imaging features.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:3 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Visualization of fibrous dysplasia during somatostatin receptor scintigraphy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.C. Chen" 1 => "F.S. Czerwiec" 2 => "P.P. Feuillan" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Nucl Med." 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68Ga-DOTA-TATE uptake in polyostotic fibrous dysplasia with McCune-Albright syndrome
Captación de 68Ga-DOTA-TATE en la Displasia Fibrosa Poliostótica con Síndrome de McCune-Albright
Khanim Niftaliyeva, Halil Turgut Turoglu
, Tunc Ones, Selin Kesim, Tanju Yusuf Erdil
Corresponding author
Department of Nuclear Medicine, Marmara University School of Medicine, Istanbul, Turkey